Methods and compositions for treating ectoparasite infestation

ABSTRACT

Compositions and methods for killing ectoparasites on a subject. Compositions containing a fatty acid ester, e.g., isopropyl myristate, effective for killing ectoparasites is described. Also described are compositions containing a fatty acid ester and a siloxane (e.g. decacyclomethicone). The compositions can also contain a mectin and/or a mycin, and S-methoprene. The compositions are useful against a variety of ectoparasites that afflict humans, animals, and plants, e.g., head lice, fleas, body lice, crab lice, scabies mites, ticks, and plant parasites.

RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 10/136,075, filed Apr. 29, 2002, the contents of which areincorporated herein in their entirety.

FIELD OF THE INVENTION

The present invention relates generally to methods and compositions forkilling ectoparasites.

BACKGROUND OF THE INVENTION

Head lice infestation is a persistent problem with as many as 6-12million people worldwide affected each year. The problem is particularlyprevalent in children with preschool and elementary-age children aged3-10 and their families becoming infested most often. Head liceinfestation is produced by the common head louse Pediculus humanuscapitis, and typically causes itching of the scalp. As the lice feed onhuman blood, they may cause lesions to develop on the scalp, swollenglands on the neck or under arms, or other symptoms. Head liceinfestation causes serious problems due to the negative socialimplications of the infestation. Body lice are also bothersome to humansand carry the additional hazard of being the vectors of certaindiseases, such as exanthematic or epidemic typhus and recurrent fever.

Various compositions are available for treating these infestations,which generally take a topical approach to treatment. Most of thesetreatments involve the use of insecticides that are harsh agents, thusraising toxicity concerns. The lice can also become resistant to theinsecticides used and therefore the compositions can lose theireffectiveness over time.

SUMMARY OF THE INVENTION

The present invention provides compositions and methods for killingectoparasites on a subject. In the most preferred embodiments, thesubject is a human and the ectoparasites are lice, fleas, and ticks. Inone embodiment, the compositions contain a fatty acid ester in an amountsufficient for killing lice, and the fatty acid ester is present as thesole agent effective for such treatment. In one embodiment, the fattyacid ester is an ester of myristate, e.g., isopropyl myristate. Inanother embodiment, the composition may also contain a siloxane, e.g.,decacyclomethicone (silicone). And in a most preferred embodiment, thecomposition contains both isopropyl myristate and decacyclomethicone anddoes not contain any other agent in an amount sufficient for killingectoparasites. In other embodiments, the compositions may also contain amectin (such as ivermectin) and/or a mycin (such as milbemycin). Infurther embodiments, the compositions also contain sesquiterpenes, suchas S-methoprene, which is effective for killing the eggs ofectoparasites, or juvenile hormone analogs (e.g., hydroprene, fenoxycarband pyriproxyfen).

In a preferred embodiment, the compositions are formulated to be appliedto the scalp of a person suffering from a head lice infestation and areleft on the treated person for a period of time. The compositions arepreferably left on the treated area for about 5-15 minutes, and morepreferably for about 10 minutes, with the effect of killing lice andtheir eggs present within 1 hour or less. In other aspects thecompositions, methods, and uses are effective for treating domestic petsfor flea infestation or for treating insect infestation of crops.

The term “subject” includes humans, plants, and mammals. The term“mammal” includes humans, and also includes animals that are members ofthe class Mammalia. This will usually be a human but also includes petssuch as dogs, cats, ferrets, rabbits, gerbils, and guinea pigs. Mammalsalso include domestic animals such as bovines, porcines, ovines, andequines. While most fur-bearing animals can become infested with fleasand ticks, pigs, horses, and cattle can also be infested with lice(e.g., the Haematopinus suis, which infests pigs, and other Haematopinusspp. that infest horses and cattle). All of these infestations aretreatable with the compositions described herein. By a topicalapplication is meant that the composition is applied to the exterior ofthe treated subject, e.g. to the exterior skin, hair, fur, or foliage.This application includes, but is not limited to, manual application orapplication by various automated means, for example, spraying orpainting onto a treated subject, or other means. By “fatty acid ester”is meant an ester composed of an organic molecule bonded to a fattyacid, e.g. isopropyl myristate. Fatty acid refers to any acid derivedfrom fats by hydrolysis and having from 6 to 22 carbon atoms. An esteris a functional derivative of a carboxylic acid, where the —OH group ofthe carboxylic acid has been replaced by an —OR, R being an alkyl group.By an “agent” is meant any compound, composition, or chemical entity. By“amount sufficient for killing” or “effective” for killing lice or otherectoparasites is meant that at least 75% of lice or ectoparasite presentare killed within 24 hours after a 10 minute exposure to thecomposition. In other embodiments, at least 90% or at least 95% or atleast 98% or at least 99% or even 100% of the lice or ectoparasitepresent on the treated subject are killed within 24 hours after a 10minute exposure to the composition. In other embodiments, the percentageof lice or other ectoparasites killed can be evaluated after 1 hourfollowing a 10 minute exposure to the composition. In one embodiment,the in vitro test described in the Examples can be used to determine the“amount sufficient” or whether a compound is “effective.” In stillfurther embodiments, the exposure time can be increased to achieve thepercentages of lice, fleas, or other ectoparasites killed, e.g. that 95%of the ectoparasites present are killed within 24 hours after a 15minute exposure, or a 30 minute exposure, or a 45 minute exposure. Asiloxane is a compound having the Si—O—Si bond, the main chemical bondfound in silica. By “infestation” is meant the presence of lice, fleas,ticks, or other ectoparasites that are the target of the treatment.Ectoparasites or pests include, but are not limited to, head lice, bodylice (e.g., Pediculus humanus), crab lice (e.g., Phthirus pubis), mites(scabies), fleas and ticks. The presence of eggs of the targetectoparasite also constitutes infestation.

The methods of the present invention include topically administering acomposition of the invention to an area on the mammal whereectoparasites are present. As noted above, the compositions preferablyremain in contact with the treated area for a period of time. In variousembodiments, no aqueous solution is applied to the treated area for atleast 10 minutes or 30 minutes or 1 hour after the topicaladministration such as, for example, by washing the treated area. Invarious embodiments the mectin and/or mycin can be replaced with anothercompound such as pyrethroids, organophosphates such as malathion anddiazinon, pyrroles, or more generally azoles, glyphosate, nicotinoids,and triazines.

Methods are also provided of manufacturing a medicament for treatingectoparasite infestation on a fur-bearing mammal. These methods involveproviding a medicament containing an above-described composition. Newuses of compositions are also provided. The medicaments are useful forkilling fleas, lice, ticks, and other pests on a mammal and contain acomposition of the present invention. The present invention alsoprovides methods of treating ectoparasite infestation on a mammal bytopically administering a composition containing ivermectin to an areaon the mammal where lice, fleas, ticks or other ectoparasites arepresent. The composition can be any of the compositions of the presentinvention, or can also be ivermectin and any suitable carrier.

The summary of the invention described above is not limiting and otherfeatures and advantages of the invention will be apparent from thefollowing detailed description of the preferred embodiments, as well asfrom the claims.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides compositions that are useful for treatingectoparasites on a mammal. The present inventors discovered unexpectedlythat just fatty acid esters alone, preferably isopropyl myristate, havethe effect of killing ectoparasites. The present inventors alsodiscovered unexpectedly that silicones (e.g., a cyclomethicone) alsohave the ability to kill ectoparasites, particularly decacyclomethicone.Thus, either or both of these may be included in a composition in anamount effective for killing lice, fleas, ticks and other ectoparasitesto result in a composition that is effective for this purpose. Isopropylmyristate was found to be a particularly effective fatty acid ester. Butthe most preferred embodiments will include both isopropyl myristate anddecacyclomethicone. These compositions offer the surprising and highlydesirable combination of benefits of being highly effective, spreadingevenly, drying quickly, having low mammalian toxicity, and being hairand skin compatible by not having a greasy or oily texture. Thereforethe compositions eliminate the disadvantages of previously availablecompositions of being messy and inconvenient to apply, emitting anunpleasant odor, having limited effectiveness, or having substantialmammalian toxicity. Thus, the present compositions can thus be appliedbefore bedtime to a human subject and, as shown in the examples herein,provide a high degree of efficacy for killing lice and otherectoparasites. Where the treated subject is a domestic animal orhousehold pet, previously available compositions suffer from pooreffectiveness, high toxicity, or are so unpleasant and cause so high alevel of discomfort if applied to the coat or fur of the treated subjectas to make them impractical to use with animals. The presentcompositions can be conveniently applied to animals and will not resultin discomfort to the animal, efforts by the animal to remove thecomposition, or result in the animal contaminating household items withthe composition, since the compositions dry quickly, spread evenly, andare of low toxicity. It is preferable that the compositions not containany alcohols since the treated patient will have bites and lesions onthe scalp or body caused by the ectoparasite, and the application ofcompositions containing alcohols will cause pain and discomfort. Thus,in the most preferred embodiments the compositions will not containaliphatic alcohols or any other alcohols.

The present invention further provides the benefit of a composition thatcan be applied for an extended period of contact. Unlike many presentlyavailable compositions which are toxic and therefore must be washed offthe treated area within minutes of application, the present compositionscan be left on the treated area for periods up to several hours ifdesired, e.g. for 5 minutes, 10 minutes, 15 minutes, 5-15 minutes, 30minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours,12 hours, or even 24 hours. The compositions can be left on the treatedarea for periods up to several hours because of the low mammaliantoxicity of the compositions of the present invention, but particularlyin the case of humans, the composition is preferably left on the treatedarea for about 10 minutes and washed off.

Other siloxanes are also useful in the present invention. The siloxaneis preferably a volatile, cyclic, non-polymeric silicone that driesquickly, spreads evenly, and does not leave a greasy residue. Examplesof siloxanes that find use in various embodiments of the invention areoctamethylcyclomethicone, cyclotetrasiloxane, cyclopentasiloxane,cyclohexasiloxane, polydimethyl siloxanes, polyalkylsiloxanes,polyethersiloxane copolymers, dimethicone, amodimethicones such astrimethylsilylamodimethicone, polysilanols, phenyl dimethicones,diphenyl dimethicones, dimethiconols, dimethicone copolyols, cetearylmethicones, hexamethyldisiloxanes, octamethylcyclotetrasiloxanes,dodecamethylcyclohexasiloxanes, and decamethylcyclopentasiloxanes. Theseare useful in various embodiments as substitutes for decacyclomethicone,or used in addition to it.

Similarly, other fatty acid esters are also useful in the presentinvention. Thus, esters of laurate, palmitate, stearate, arachidate,behenate, and lignocerate, or fatty acid esters containing anunsaturated bond, such as for example palmitoleate, oleate, linoleate,linolenate, and arachidonate are also useful in the invention assubstitutes for myristate or used in addition to myristate. And fattyacid esters containing one or more unsaturated bonds are alsocontemplated in the invention, e.g., fatty acids containing one, two, orthree unsaturated bonds such as linoleic, linolenic, palmitoleic,arachidoneic acids. Preferred esters for use in the invention includealkyl esters and alcohol esters. Preferred esters include isopropylesters, methyl esters, ethyl esters, and propyl esters. The presentinvention also provides methods of killing lice, fleas, ticks, and otherectoparasites on a treated subject by topically administering to an areaon the subject where the ectoparasites are present a compositions of oneor more of these siloxanes. The siloxane is provided in an amountsufficient to kill ectoparasites present.

Other compounds can be included in the compositions of the presentinvention. For example sesquiterpenes (preferably S-methoprene), whichkills the eggs of ectoparasites (e.g., lice and fleas), may be includedto enhance the potency of the compositions by also killing eggs that maybe present on the treated person. Addition of S-methoprene or anothersesquiterpene or a juvenile hormone analog will aid the killing of eggs,therefore facilitating effective treatment and eliminating the need totreat the patient repeatedly. In preferred embodiments that contain asesquiterpene, the composition contains the fatty acid ester and/or thesiloxane, and the sesquiterpene, and does not contain any other agent inan amount sufficient for killing fleas or lice present. An acid maydesirably be included in the formulation to assist in lowering the pH ofthe formulation, which will facilitate the removal of eggs that arecemented to hair or skin. The acids can be added to the formulationsuntil the pH reaches about 4. Organic acids such as lactic acid, diluteacetic acid or glacial acetic acid, citric acid, are non-injurious acidsthat are useful for this purpose. Dilute hydrochloric acid can also beused. In other embodiments, the compositions contain no acids, orcontain less than 1.0% acid.

The present inventors discovered unexpectedly that ivermectin is able tokill head lice and their eggs when topically applied. Thus, the presentinvention provides compositions and methods of treating ectoparasites(e.g., lice and fleas) by topically applying a composition containingivermectin to the area to be treated. In one embodiment, the compositionwill contain ivermectin and will not contain any other agent in anamount sufficient for killing ectoparasites present. The person ofordinary skill in the art will realize that various compounds areavailable to act as carriers of the ivermectin. The ivermectin can alsobe included in any of the compositions of the present invention. Forexample, the ivermectin can be included in a composition with one ormore of the fatty acid, the siloxane, and the sesquiterpene, and thecomposition will not contain any additional agent in an amountsufficient for killing ectoparasites present.

The present compositions and methods can also be useful for treatingflea and tick infestations on household pets. Any mammalian pet may betreated using these methods (e.g., a dog or cat). The compositionsspread evenly and with little effort, and dry quickly. Thus, they may beconveniently used with great effectiveness and little or no discomfortto the treated animal. The methods and compositions may also be used totreat ectoparasites such as fleas and ticks on domestic animals such asbovines, equines, porcines, ovines, etc. The person of ordinary skill inthe art will realize that animals are primarily subject to flea and tickinfestations but that porcines and other domestic animals are alsosubject to tick and lice infestations (known as Haematopinus spp.), andthat the present compositions will be effective for both.

The present invention can also be useful for treating plant parasiteinfestations in plants and crops. The invention may be particularlyuseful in the context of a greenhouse, where individual plants may betreated with a composition of the present invention to destroy aphids,or other plant parasites such as, for example, white flies, spidermites, and other sucking insects. Other preferred applications includehigh value or ornamental plants, where undamaged foliage is ofparticular importance, or plants that bear fruit that is more desirableif undamaged. Such damage is frequently a result of applying chemicalinsecticides or pediculocides, which dry on the foliage, or is theresult of the plant parasite activity. The methods involve topicallyapplying a composition of the present invention to the plant to betreated. The compositions of the present invention have no detrimentalaffect on the treated plant. In various embodiments of the presentinvention, it may be desirable to utilize a composition containing asiloxane and a fatty acid ester as a carrier with the addition of otheractive compounds. For example, the siloxane and fatty acid estercomposition may be useful as a carrier of fungicides, insecticides, orherbicides, because it possesses the desirable properties of dryingquickly, spreading easily and evenly, and does not “burn” or otherwisecause damage to the crops, foliage, or fruit. Pesticides, specificallyfungicides, herbicides, and insecticides that are not soluble in watercan be applied advantageously using the present invention. For example,pyrethroids, organophosphates such as malathion and diazinon, pyrroles,or more generally azoles, glyphosate, nicotinoids, and triazines may beapplied using a composition of the present invention.

In the context of application to livestock or domestic animals, thecompositions contain no solvents that are irritating to the treatedanimals. Permethrin, macrolides such as ivermectin, doramectin,moxidectin, abamectin, emamectin, eprinomectin, mycins such asmilbemycin, and fungicides such as the azoles can be applied with asiloxane and a fatty acid ester as the carrier and spreader. The azolescan include the imidazoles and the triazoles. The imidazoles include,for example, clotrimazole, miconazole, ketoconazole, econazole, andsulconazole. The triazoles include, for example, itraconazole andfluconazole.

In the compositions of the present invention a mixture of about 50%fatty acid ester and about 50% siloxane (w/w) is preferable. But theactual amounts of the ingredients may vary substantially. For example,the composition can also be at least about 10%, about 20%, about 30%,about 40%, about 50%, about 60%, about 70%, about 80%, or about 90%fatty acid ester, and the remainder the siloxane. Alternatively, thecomposition may be at least about 10%, about 20%, about 30%, about 40%,about 50%, about 60%, about 70%, about 80% or about 90% siloxane and theremainder the fatty acid ester. Preferred amounts of the siloxane alsoinclude between 45% and 55% (w/w), between 40% and 60%, between 30% and70%, between 25% and 70%, and between 35% and 65%. It is preferred thatthe fatty acid ester be present at less than 65% or 70% w/w and at morethan 20%, 25%, or 35%, and most preferably at about 50%±5% (w/w) orabout 49.5% w/w. Other preferable amounts of the fatty acid esterinclude from about 40% to about 60% or from about 25% to 65% or between45% and 55%, between 30% and 70%, between 35% and 65%, between 25% and65%, or between 25% and 70% (w/w). Preferred amounts of the siloxane arebetween 25% and 75% or between 30% and 70% or between 35% and 65% orbetween 40% and 60% and most preferably at about 50% or 49.5%. In oneembodiment the composition contains about 50% isopropyl myristate andabout 50% siloxane and does not contain any other ingredients. Inembodiments where additional ingredients are desired, such asS-methoprene, ivermectin, or a pesticide, these may be included indesired proportions while subtracting the siloxane and/or fatty acidester accordingly. When S-methoprene is included in the composition, itmay be present from about 0.02% to about 2.0% or even higher, butpreferably will be included at about 0.2% (w/w) or 0.4% (w/w) or 0.6%(w/w) or 0.8% (w/w). When ivermectin is included it may desirably bepresent from about 0.02% to about 1.0%, and preferably will be presentat about 0.2%.

In other embodiments the fatty acid ester is present in the compositionwith a pharmaceutically acceptable carrier. While the siloxane is apreferred carrier because it spreads evenly, dries quickly, has lowmammalian toxicity, and is believed to act synergistically with thefatty acid ester to kill ectoparasites, persons of ordinary skill in theart will realize that other pharmaceutically acceptable carriers arealso useful. In these embodiments the fatty acid ester is used at theconcentrations described above, with the rest of the composition beingone or more carriers or other ingredients as desired.

The present invention also provides kits for treating ectoparasiteinfestations. In various embodiments the kits include a composition ofthe present invention in a package or other enclosure. In otherembodiments the kits further include a “nit comb” to assist in removingectoparasites (e.g. lice) and their eggs from hair. The “nit comb” is anordinary comb for ordering hair by passing it through the hair. Forexample the LICEMEISTER® (National Pediculosis Association, Inc.,Newton, Mass.), ACU-MED® Lice Comb (Health Enterprises, N. Attleboro,Mass.), MEDI-SWEEP Lice Comb (Classic Products, Oxnard, Calif.) arepreferred embodiments of the lice comb to be included in the kit. Thepackage can be a box, or may simply be a wrapping (preferably of aplastic) that surrounds the kit. The comb is preferably provided insidethe package, but can also be attached to the outside of the package. Inother embodiments the kits include markers such as fluorescent dyes, orshower caps. In preferred embodiments the kit also contains instructionsthat describe how to use the items included in the kit to killectoparasites.

Further embodiments of the present invention are described in thefollowing examples.

EXAMPLE 1 Formulations

The most preferred formulations of the present invention are comprisedof a 50:50 mixture of a cyclomethicone and isopropyl myristate (w/w). Invarious embodiments ivermectin can be added at about 0.2% (w/w), and/orS-methoprene at about 0.8% (w/w), for embodiments where their additionis desirable. The person of ordinary skill will realize that the amountsstated here may be varied significantly or substitutions made and thecomposition will still retain its desirable properties. For example, thecyclomethicone may preferably be ST-Cyclomethicone-5 NF™ (DOW CORNING®,Midland, Mich.).

ST-Cyclomethicone 5-NF™ is clear, colorless, volatilepolydimethylcyclosiloxane composed mainly ofdecamethylcyclopentasiloxane (D5), which is present at greater than 95%.The octamethylcyclotetrasiloxane (D4) is present at values less than 1%in ST-Cyclomethicone 5™. Other types of siloxanes have differentcompositions. For example cyclomethicone 344 fluid (DOW CORNING®)contains a higher portion of the octamethylcyclomethicone, and is alow-viscosity polydimethylcyclosiloxane fluid. In the present inventionthe use of the decamethylcyclopentasiloxane (D5) is preferred, and mostpreferably is present in the siloxane at concentrations of at least 30%,35%, 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or even presentat 100% decamethylcyclopentasiloxane. It has been found that thedecamethylcyclopentasiloxane (D5) is a particularly preferred siloxanefor killing ectoparasites. Without wanting to be bound by any particulartheory it is believed that the decamethylcyclopentasiloxane (D5) actssynergistically with the fatty acid ester, and in particular isopropylmyristate, to result in a composition with higher ectoparasite killingpowers and properties.

Isopropyl myristate (IPM), NF is known chemically as1-methylethyltetradecanoate with an empirical formula of C₁₇H₃₄O₂ andmolecular weight of 270.51. It is prepared by the esterification ofmyristic acid with propan-2-ol, (isopropyl ester of myristic acid).

In those embodiments comprising only myristate, the myristate can beused at 100% or mixed with another desirable carrier other than asiloxane. Desirable carriers are known to those of ordinary skill in thearts. Examples of carriers include ethanol, polyols, alcohols, triethylcitrate, polyethylene glycol, castor oil, cottonseed oil, acetone,chloroform, and ethyl acetate.

The present invention eliminates the need for the inclusion of chemicalsand agents that are undesirable for the reasons stated herein. Thus,most preferably the compositions do not contain any of the followingcompounds: pyrethrin, pyrethroid, permethrin, lindane, malathion,carbaryl, carbaryl malathion, phenothrin, spinosyns, plant oils (e.g.,those from the genera Salvia, Artemisia, Citrus, Juniperus, Laurus,Myristica, Origanum, Piper or Aloysia), anise oil, tea tree oil, lemonoil, almond oil, cocoa butter, theobroma oil, aromatic oils,hydrogenated animal fats and hydrogenated vegetable oils, esters ofpolyalcohols, sugar fatty acid esters (e.g., esters of sucrose,fructose, maltose, lactose and other monosaccharides and disaccharides),1-[N-(halo-3-pyridylmethyl)-N-methylamino-1-akylamino-2-nitroethylenederivatives, nicotinergic acetylcholine receptor agonists orantagonists, citronellal, citronellol, citronellyl, lactoperoxidase,thiocyanate, iodide, hydrogen peroxide sources, phenyl C₂₋₆ alkanols,phenyl C₂₋₆ diols, C₂₋₈ alkylene diols, alcohols, including non-volatilefatty alcohols (e.g., C₁₂-C₁₆ alcohols, ceteryl alcohol, cetyl alcohol,isostearyl alcohol, lanolin alcohol, lauryl alcohol, olelyl alcohol,stearyl alcohol), aliphatic alcohols (such as for example propanol,isopropanol, butanol, t-butyl alcohol, pentanol, octanol, ethanol),anionic or cationic surfactants (e.g., sodium or ammonium laurylsulfate, sodium or ammonium laureth sulfate, quaternary ammonium saltssuch as those listed in U.S. Pat. No. 5,288,483, anionic surfactantssuch as those listed in U.S. Pat. No. 6,342,482, tallow propanediammonium dichloride, dialkyldimethylammonium chlorides, fatty amines),ammonium hydroxide, other anionic agents, glyceryl esters (e.g., mono-,di-, and triglycerides), parabens such as methylparaben, propylparaben,and butylparaben, alkylene glycols (e.g., ethylene glycol, propyleneglycol,), polyalkylene glycols, polyalkylene oxides, polyols (e.g.,glycerol), amphoteric agents (e.g., sodium 3-dodecylaminopropionate,sodium 3-dodecylaminopropane sulfonate, N-alkyltaurines), zwitterionicsurfactants (e.g., aliphatic quaternary ammonium, phosphonium, andsulfonium compounds, betaines), and nonionic surfactants (e.g.,polyethylene oxide condensates of alkyl phenols, condensates of ethyleneoxide with a product of the reaction of propylene oxide and ethylenediamine products, the condensation product of aliphatic alcohols havingfrom 8 to 18 carbon atoms, long chain tertiary amine oxides, long chaintertiary phosphine oxides, long chain dialkyl sulfoxides), sorbitantristearate, sorbitan monopalmitate, sodium bis-(2-ethylhexyl),sulfosuccinate, butylene glycol distearate, polysorbate 80, tocopherols,glyceryl esters (e.g., mono-, di- and triglycerides), polyalkyleneglycols (e.g., propylene glycol, polyethylene glycol), sorbitan,sucrose, citric acid, citric acid, acetic acid, lauroamphoglycinate,PEG-150 distearate, quaternium 15, benzimidazoles, acid salts ofdemecarium, echothiopate, edrophonium, neostigmine, pyridostigmineambenonium, and isofluorophate, diethyltoluamide, piperonal,alkylcelluloses, zinc 2-pyridinethiol 1-oxide, cellulose derivatives,tallow, lard, suet, butter, and wool fat. In preferred embodiments thecomposition is a non-aqueous formulation that contains less than 10% or5% or 2% or 1% water, or contains no water. But in other embodiments,some amount of any of the ingredients listed above may be present tosuit a particular purpose, for example, less than 10% or less than 5% orless than 3% or less than 2% or less than 1% or less than 0.5% or lessthan 0.25% or less than 0.1% or less than 0.05% or less than 0.025% orless than 0.01% or less than 0.005% (w/w) of any of these ingredientscan be present, as desired.

The following presents a preferred procedure for preparing a preferredcomposition of the present invention. In this embodiment a compositionof the invention was prepared containing the following:

ST-Cyclomethicone 5, NF ™ 49.5% Isopropyl Myristate, NF 49.5 Ivermectin 0.2 S-Methoprene  0.8

The ST-Cyclomethicone-5™ and isopropyl myristate were combined in asteel mixing vessel equipped with an air-driven mixing shaft andimpellor. The ivermectin was added into the mixing vortex of thecyclomethicone and isopropyl myristate. Heat was applied at 30° C., andthe mixing continued for 30 minutes to dissolve the ivermectin. The heatsource was removed and S-methoprene (when desirable for the embodiment)was added with continued mixing. The total was mixed for 15-20 minutesat low to medium speed to prevent incorporation of air. The product canbe stored in an enclosed cover stainless steel storage tank atcontrolled room temperatures 15-30° C. until packaging.

EXAMPLE 2 Procedure for Evaluating Compositions for Killing Lice

In this embodiment, the effectiveness of pediculicidal materials in theformulation of Example 1 is examined against the adult body louse,Pediculus humanus humanus. But this procedure can be used to test theeffectiveness of a composition against the head louse, fleas, ticks, orany ectoparasite. In the following description, “morbid” means that thelouse is unable to move towards heat 1 h after treatment. The parasiteis sick but not necessarily dying, and may recover to resume normalbehavior within 24 hours. By “moribund” is meant the parasite is unableto move towards heat (and therefore food) 24 hours after treatment andis dying.

Four replicates of 25 lice each, plus five control replicates wereexamined. A plastic or glass vial, screened at the bottom with 20-meshwas used as the dipping vessel. A plunger, made from a plastic rod, anda circular screen was fitted inside the vial.

25 adult lice of mixed sexes were placed in the bottom of a testcontainer. A screened plunger was inserted to keep the lice fromfloating to the surface. The pediculicide material to be tested wasplaced in a 100-ml beaker and the beaker introduced into a water bathmaintained at 32° C. The test container was placed into the pediculicidein the 100-ml beaker and the lice kept under the pediculicide for 1, 4or 10 minutes. The test container was removed at end of the desireddipping period.

The test container was dipped into a beaker containing distilled waterat 32° C. and the container agitated. At the end of 1 minute, thecontainer was removed and the lice washed gently in a stream ofdistilled water (32° C.) from a wash bottle. The lice were transferredto a clean patch of cloth, which was then placed in a petri dish. Thepetri dish with the lice was incubated at 31.7° C. and 60% relativehumidity.

After 1 hour, an observation was made and the dish replaced.Observations were made by placing the cloth with the lice on top of aclean cloth on the plate. The plate was then placed on a slide warmer(37° C.) to generate a heat source for attracting the lice. Lice thatwere not dead or morbid moved to the lower patch (i.e., towards heat)within 5 minutes. Observations were repeated at the appropriateintervals.

EXAMPLE 3 Effect of Compositions on Ectoparasites

Utilizing the procedure described above, the following observations werenoted. Exposure of body lice to a composition of cyclomethicone (DowCorning 344® fluid) and isopropyl myristate (50/50 w/w) for 10 minutesresulted in about 52% of the lice being killed within 1 hour and over99% mortality of lice after 24 hours.

Exposure of the body lice to a composition of 100% cyclomethicone (DowCorning 344® Fluid) for 10 minutes resulted in 100% morbidity of thelice after 1 hour, and about 16% mortality of the lice after 24 hours.

Exposure of the body lice to a composition of 100% ST-Cyclomethicone 5™,for 10 minutes resulted in 100% morbidity of the lice after 1 hour, andabout 79% mortality of the lice after 24 hours.

It was observed that exposure of body lice to a composition of 100%isopropyl myristate for 10 minutes resulted in about 82% mortality after1 hour, with the rest of the lice being morbid. After 24 hours, themortality rate was 100%.

For all assays, the control mortality was 15% and the controlcomposition was water.

EXAMPLE 4 Ovicidal Formulations

In this example the formulations were examined in an embodiment where anovicide was also included in the formulation. Often the effectiveness ofan ovicide can be assessed not only by the percentage of eggs that failto hatch (or eclose) but also on the stage of embryo development wherefurther differentiation of the larvae is arrested by the action of thecompound. Natural mortality should cause equal numbers of non-viableeggs or larvae at each stage of development, although this may becomeapparent only with large population sizes.

In this embodiment, ivermectin was included at 0.20% in the formulationcontaining ST-cyclomethicone 5, isopropyl myristate (49.9/49.9), andS-methoprene at 0.2%. When lice eggs were contacted with the formulationfor 10 minutes, about 44% of the eggs were killed, meaning that the eggsfailed to hatch or that they were in emergent stage with the nymphskilled. Nearly 90% of the eggs killed were arrested in the early or latestage of development (as opposed to emergent stage). 24 hours after a 10minute exposure, all lice were dead. By early stage is meant there is novisible differentiation of the embryo. By late stage is meant eye spotsand/or limbs are visible through the chorion of the egg. By emergentstage is meant fully formed nymphs are visible in the process ofemerging, but not yet separated from the egg.

EXAMPLE 5 Ticks

A composition of the present invention containing ST-Cyclomethicone-5™and isopropyl myristate (50/50), ivermectin at 0.20%, and S-methopreneat 0.2% was utilized. Twenty four R. sanguineus ticks were soaked for 10minutes in pediculocide dip (using water as a control) and patted dry.At one hour and 24 hours the numbers of live and dead ticks werecounted. 100% of ticks were killed within 1 hour by the 10 minuteexposure to the formulation, while none of the control group ticks werekilled.

The invention illustratively described herein may be practiced in theabsence of any element or elements, limitation or limitations which isnot specifically disclosed herein. The terms and expressions which havebeen employed are used as terms of description and not of limitation,and there is no intention that in the use of such terms and expressionsof excluding any equivalents of the features shown and described orportions thereof, but it is recognized that various modifications arepossible within the scope of the invention claimed. Thus, it should beunderstood that although the present invention has been specificallydisclosed by preferred embodiments and optional features, modificationand variation of the concepts herein disclosed may be resorted to bythose skilled in the art, and that such modifications and variations areconsidered to be within the scope of this invention as defined by theappended claims.

The contents of the articles, patents, and patent applications, and allother documents and electronically available information mentioned orcited herein, are hereby incorporated by reference in their entirety tothe same extent as if each individual publication was specifically andindividually indicated to be incorporated by reference. Applicantsreserve the right to physically incorporate into this application anyand all materials and information from any such articles, patents,patent applications, or other documents.

The inventions illustratively described herein may suitably be practicedin the absence of any element or elements, limitation or limitations,not specifically disclosed herein. Thus, for example, the terms“comprising”, “including,” containing”, etc. shall be read expansivelyand without limitation. Additionally, the terms and expressions employedherein have been used as terms of description and not of limitation, andthere is no intention in the use of such terms and expressions ofexcluding any equivalents of the features shown and described orportions thereof, but it is recognized that various modifications arepossible within the scope of the invention claimed. Thus, it should beunderstood that although the present invention has been specificallydisclosed by preferred embodiments and optional features, modificationand variation of the inventions embodied therein herein disclosed may beresorted to by those skilled in the art, and that such modifications andvariations are considered to be within the scope of this invention.

The invention has been described broadly and generically herein. Each ofthe narrower species and subgeneric groupings falling within the genericdisclosure also form part of the invention. This includes the genericdescription of the invention with a proviso or negative limitationremoving any subject matter from the genus, regardless of whether or notthe excised material is specifically recited herein.

In addition, where features or aspects of the invention are described interms of Markush groups, those skilled in the art will recognize thatthe invention is also thereby described in terms of any individualmember or subgroup of members of the Markush group.

Other embodiments are set forth within the following claims.

1. A method of killing ectoparasites on a subject, said methodcomprising: topically administering an alcohol-free, insecticide-free,polysorbate 80-free composition to an area on the subject whereectoparasites are present, wherein the composition comprises a carrierand an ectoparasiticidal agent consisting essentially of isopropylmyristate at a concentration between 35% and 70% w/w, and whereinfurther at least 82% of the ectoparasites are killed within 1 hour afteradministration of the composition and retention thereof on the treatedarea for 10 minutes.
 2. The method according to claim 1, wherein saidectoparasites are selected from the group consisting of lice, mites,ticks, and fleas.
 3. The method according to claim 2, wherein thesubject is a mammal.
 4. The method according to claim 3, wherein themammal is a human and the ectoparasites are head lice.
 5. The method ofclaim 1, further comprising the step of combing killed ectoparasites outof the subject's hair with a nit comb.